Evaluation of a new point-of-care oral anti-HCV test for screening of hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is a public health issue for which an effective universal screening method is urgently needed. An oral anti-HCV test could provide a noninvasive and rapid screening strategy for HCV infection. This study evaluated the performance of a new point-of-care oral assay developed by Well for the detection of HCV antibody. METHODS: Individuals from three centers with and without HCV infection were enrolled. All participants were tested for oral HCV antibody using the Well assay and for serum HCV antibody using established tests (ARCHITECT i2000 anti-HCV assay and InTec serum anti-HCV assay). For participants who obtained positive results, HCV RNA was tested for verification. Some patients underwent the OraQuick HCV test at the same time, and some self-tested with the Well assay during the same period. RESULTS: A total of 1179 participants, including 486 patients with chronic HCV infection, 108 patients with other liver diseases, and 585 individuals who underwent physical examination, were enrolled. The Well anti-HCV test had a sensitivity of 91.88% (95% confidence interval [CI]: 88.97-94.09%) and a specificity of 98.00% (96.58-98.86%) for oral HCV antibody detection. The consistency between the Well and InTec assays was 97.02% (1138/1179). The consistency between the Well and OraQuick assays was 98.50% (197/200). Furthermore, the results of self-testing were highly consistent with those of researcher-administered tests (Kappa = 0.979). In addition, the HCV RNA results also showed that HCV RNA could only be detected on 1 of the 39 false-negative samples, and for 172 positive HCV RNA results, 171 could be detected by the Well oral anti-HCV assay. CONCLUSIONS: The Well oral anti-HCV test offers high sensitivity and specificity and performed comparably to both the OraQuick assay and InTec assay for HCV diagnosis. Thus, the Well test represents a new tool for universal HCV screening to identify infected patients, particularly in regions with limited medical resources.

Ultrafast Graphene Light Emitters.

Ultrafast electrically driven nanoscale light sources are critical components in nanophotonics. Compound semiconductor-based light sources for the nanophotonic platforms have been extensively investigated over the past decades. However, monolithic ultrafast light sources with a small footprint remain a challenge. Here, we demonstrate electrically driven ultrafast graphene light emitters that achieve light pulse generation with up to 10 GHz bandwidth across a broad spectral range from the visible to the near-infrared. The fast response results from ultrafast charge-carrier dynamics in graphene and weak electron-acoustic phonon-mediated coupling between the electronic and lattice degrees of freedom. We also find that encapsulating graphene with hexagonal boron nitride (hBN) layers strongly modifies the emission spectrum by changing the local optical density of states, thus providing up to 460% enhancement compared to the gray-body thermal radiation for a broad peak centered at 720 nm. Furthermore, the hBN encapsulation layers permit stable and bright visible thermal radiation with electronic temperatures up to 2000 K under ambient conditions as well as efficient ultrafast electronic cooling via near-field coupling to hybrid polaritonic modes under electrical excitation. These high-speed graphene light emitters provide a promising path for on-chip light sources for optical communications and other optoelectronic applications.

Thermoelectric detection and imaging of propagating graphene plasmons.

Controlling, detecting and generating propagating plasmons by all-electrical means is at the heart of on-chip nano-optical processing. Graphene carries long-lived plasmons that are extremely confined and controllable by electrostatic fields; however, electrical detection of propagating plasmons in graphene has not yet been realized. Here, we present an all-graphene mid-infrared plasmon detector operating at room temperature, where a single graphene sheet serves simultaneously as the plasmonic medium and detector. Rather than achieving detection via added optoelectronic materials, as is typically done in other plasmonic systems, our device converts the natural decay product of the plasmon-electronic heat-directly into a voltage through the thermoelectric effect. We employ two local gates to fully tune the thermoelectric and plasmonic behaviour of the graphene. High-resolution real-space photocurrent maps are used to investigate the plasmon propagation and interference, decay, thermal diffusion, and thermoelectric generation.

Terahertz Nanofocusing with Cantilevered Terahertz-Resonant Antenna Tips.

We developed THz-resonant scanning probe tips, yielding strongly enhanced and nanoscale confined THz near fields at their tip apex. The tips with length in the order of the THz wavelength (λ = 96.5 µm) were fabricated by focused ion beam (FIB) machining and attached to standard atomic force microscopy (AFM) cantilevers. Measurements of the near-field intensity at the very tip apex (25 nm radius) as a function of tip length, via graphene-based (thermoelectric) near-field detection, indicate their first and second order geometrical antenna resonances for tip length of 33 and 78 µm, respectively. On resonance, we find that the near-field intensity is enhanced by one order of magnitude compared to tips of 17 µm length (standard AFM tip length), which is corroborated by numerical simulations that further predict remarkable intensity enhancements of about 107 relative to the incident field. Because of the strong field enhancement and standard AFM operation of our tips, we envision manifold and straightforward future application in scattering-type THz near-field nanoscopy and THz photocurrent nanoimaging, nanoscale nonlinear THz imaging, or nanoscale control and manipulation of matter employing ultrastrong and ultrashort THz pulses.

Frictional Magneto-Coulomb Drag in Graphene Double-Layer Heterostructures.

Coulomb interaction between two closely spaced parallel layers of conductors can generate the frictional drag effect by interlayer Coulomb scattering. Employing graphene double layers separated by few-layer hexagonal boron nitride, we investigate density tunable magneto- and Hall drag under strong magnetic fields. The observed large magnetodrag and Hall-drag signals can be related with Laudau level filling status of the drive and drag layers. We find that the sign and magnitude of the drag resistivity tensor can be quantitatively correlated to the variation of magnetoresistivity tensors in the drive and drag layers, confirming a theoretical formula for magnetodrag in the quantum Hall regime. The observed weak temperature dependence and ∼B^{2} dependence of the magnetodrag are qualitatively explained by Coulomb scattering phase-space argument.

Highly confined low-loss plasmons in graphene-boron nitride heterostructures.

Graphene plasmons were predicted to possess simultaneous ultrastrong field confinement and very low damping, enabling new classes of devices for deep-subwavelength metamaterials, single-photon nonlinearities, extraordinarily strong light-matter interactions and nano-optoelectronic switches. Although all of these great prospects require low damping, thus far strong plasmon damping has been observed, with both impurity scattering and many-body effects in graphene proposed as possible explanations. With the advent of van der Waals heterostructures, new methods have been developed to integrate graphene with other atomically flat materials. In this Article we exploit near-field microscopy to image propagating plasmons in high-quality graphene encapsulated between two films of hexagonal boron nitride (h-BN). We determine the dispersion and plasmon damping in real space. We find unprecedentedly low plasmon damping combined with strong field confinement and confirm the high uniformity of this plasmonic medium. The main damping channels are attributed to intrinsic thermal phonons in the graphene and dielectric losses in the h-BN. The observation and in-depth understanding of low plasmon damping is the key to the development of graphene nanophotonic and nano-optoelectronic devices.

High-Responsivity Graphene-Boron Nitride Photodetector and Autocorrelator in a Silicon Photonic Integrated Circuit.

Graphene and other two-dimensional (2D) materials have emerged as promising materials for broadband and ultrafast photodetection and optical modulation. These optoelectronic capabilities can augment complementary metal-oxide-semiconductor (CMOS) devices for high-speed and low-power optical interconnects. Here, we demonstrate an on-chip ultrafast photodetector based on a two-dimensional heterostructure consisting of high-quality graphene encapsulated in hexagonal boron nitride. Coupled to the optical mode of a silicon waveguide, this 2D heterostructure-based photodetector exhibits a maximum responsivity of 0.36 A/W and high-speed operation with a 3 dB cutoff at 42 GHz. From photocurrent measurements as a function of the top-gate and source-drain voltages, we conclude that the photoresponse is consistent with hot electron mediated effects. At moderate peak powers above 50 mW, we observe a saturating photocurrent consistent with the mechanisms of electron-phonon supercollision cooling. This nonlinear photoresponse enables optical on-chip autocorrelation measurements with picosecond-scale timing resolution and exceptionally low peak powers.

High-speed electro-optic modulator integrated with graphene-boron nitride heterostructure and photonic crystal nanocavity.

Nanoscale and power-efficient electro-optic (EO) modulators are essential components for optical interconnects that are beginning to replace electrical wiring for intra- and interchip communications.1-4 Silicon-based EO modulators show sufficient figures of merits regarding device footprint, speed, power consumption, and modulation depth.5-11 However, the weak electro-optic effect of silicon still sets a technical bottleneck for these devices, motivating the development of modulators based on new materials. Graphene, a two-dimensional carbon allotrope, has emerged as an alternative active material for optoelectronic applications owing to its exceptional optical and electronic properties.12-14 Here, we demonstrate a high-speed graphene electro-optic modulator based on a graphene-boron nitride (BN) heterostructure integrated with a silicon photonic crystal nanocavity. Strongly enhanced light-matter interaction of graphene in a submicron cavity enables efficient electrical tuning of the cavity reflection. We observe a modulation depth of 3.2 dB and a cutoff frequency of 1.2 GHz.

High-contrast electrooptic modulation of a photonic crystal nanocavity by electrical gating of graphene.

We demonstrate high-contrast electro-optic modulation of a photonic crystal nanocavity integrated with an electrically gated monolayer graphene. A silicon air-slot nanocavity provides strong overlap between the resonant optical field and graphene. Tuning the Fermi energy of the graphene layer to 0.85 eV enables strong control of its optical conductivity at telecom wavelengths, which allows modulation of cavity reflection in excess of 10 dB for a swing voltage of only 1.5 V. The cavity resonance at 1570 nm is found to undergo a shift in wavelength of nearly 2 nm, together with a 3-fold increase in quality factor. These observations enable a cavity-enhanced determination of graphene's complex optical sheet conductivity at different doping levels. Our simple device demonstrates the feasibility of high-contrast, low-power, and frequency-selective electro-optic modulators in graphene-integrated silicon photonic integrated circuits.

Strong enhancement of light-matter interaction in graphene coupled to a photonic crystal nanocavity.

We demonstrate a large enhancement in the interaction of light with graphene through coupling with localized modes in a photonic crystal nanocavity. Spectroscopic studies show that a single atomic layer of graphene reduces the cavity reflection by more than a factor of one hundred, while also sharply reducing the cavity quality factor. The strong interaction allows for cavity-enhanced Raman spectroscopy on subwavelength regions of a graphene sample. A coupled-mode theory model matches experimental observations and indicates significantly increased light absorption in the graphene layer. The coupled graphene-cavity system also enables precise measurements of graphene's complex refractive index.

Renormalization of the graphene dispersion velocity determined from scanning tunneling spectroscopy.

In graphene, as in most metals, electron-electron interactions renormalize the properties of electrons but leave them behaving like noninteracting quasiparticles. Many measurements probe the renormalized properties of electrons right at the Fermi energy. Uniquely for graphene, the accessibility of the electrons at the surface offers the opportunity to use scanned probe techniques to examine the effect of interactions at energies away from the Fermi energy, over a broad range of densities, and on a local scale. Using scanning tunneling spectroscopy, we show that electron interactions leave the graphene energy dispersion linear as a function of excitation energy for energies within ±200 meV of the Fermi energy. However, the measured dispersion velocity depends on density and increases strongly as the density approaches zero near the charge neutrality point, revealing a squeezing of the Dirac cone due to interactions.

Thermal radiation control from hot graphene electrons coupled to a photonic crystal nanocavity.

Controlling thermal radiation is central in a range of applications including sensing, energy harvesting, and lighting. The thermal emission spectrum can be strongly modified through the electromagnetic local density of states (EM LDOS) in nanoscale-patterned metals and semiconductors. However, these materials become unstable at high temperature, preventing improvements in radiative efficiency and applications such as thermophotovoltaics. Here, we report stable high-temperature thermal emission based on hot electrons (>2000 K) in graphene coupled to a photonic crystal nanocavity, which strongly modifies the EM LDOS. The electron bath in graphene is highly decoupled from lattice phonons, allowing a comparatively cool temperature (700 K) of the photonic crystal nanocavity. This thermal decoupling of hot electrons from the LDOS-engineered substrate opens a broad design space for thermal emission control that would be challenging or impossible with heated nanoscale-patterned metals or semiconductor materials.

Fast thermal relaxation in cavity-coupled graphene bolometers with a Johnson noise read-out.

High sensitivity, fast response time and strong light absorption are the most important metrics for infrared sensing and imaging. The trade-off between these characteristics remains the primary challenge in bolometry. Graphene with its unique combination of a record small electronic heat capacity and a weak electron-phonon coupling has emerged as a sensitive bolometric medium that allows for high intrinsic bandwidths1-3. Moreover, the material's light absorption can be enhanced to near unity by integration into photonic structures. Here, we introduce an integrated hot-electron bolometer based on Johnson noise readout of electrons in ultra-clean hexagonal-boron-nitride-encapsulated graphene, which is critically coupled to incident radiation through a photonic nanocavity with Q = 900. The device operates at telecom wavelengths and shows an enhanced bolometric response at charge neutrality. At 5 K, we obtain a noise equivalent power of about 10 pW Hz-1/2, a record fast thermal relaxation time, <35 ps, and an improved light absorption. However the device can operate even above 300 K with reduced sensitivity. We work out the performance mechanisms and limits of the graphene bolometer and give important insights towards the potential development of practical applications.

Tuning quantum nonlocal effects in graphene plasmonics.

The response of electron systems to electrodynamic fields that change rapidly in space is endowed by unique features, including an exquisite spatial nonlocality. This can reveal much about the materials' electronic structure that is invisible in standard probes that use gradually varying fields. Here, we use graphene plasmons, propagating at extremely slow velocities close to the electron Fermi velocity, to probe the nonlocal response of the graphene electron liquid. The near-field imaging experiments reveal a parameter-free match with the full quantum description of the massless Dirac electron gas, which involves three types of nonlocal quantum effects: single-particle velocity matching, interaction-enhanced Fermi velocity, and interaction-reduced compressibility. Our experimental approach can determine the full spatiotemporal response of an electron system.

Acoustic terahertz graphene plasmons revealed by photocurrent nanoscopy.

Terahertz (THz) fields are widely used for sensing, communication and quality control. In future applications, they could be efficiently confined, enhanced and manipulated well below the classical diffraction limit through the excitation of graphene plasmons (GPs). These possibilities emerge from the strongly reduced GP wavelength, λp, compared with the photon wavelength, λ0, which can be controlled by modulating the carrier density of graphene via electrical gating. Recently, GPs in a graphene/insulator/metal configuration have been predicted to exhibit a linear dispersion (thus called acoustic plasmons) and a further reduced wavelength, implying an improved field confinement, analogous to plasmons in two-dimensional electron gases (2DEGs) near conductive substrates. Although infrared GPs have been visualized by scattering-type scanning near-field optical microscopy (s-SNOM), the real-space imaging of strongly confined THz plasmons in graphene and 2DEGs has been elusive so far-only GPs with nearly free-space wavelengths have been observed. Here we demonstrate real-space imaging of acoustic THz plasmons in a graphene photodetector with split-gate architecture. To that end, we introduce nanoscale-resolved THz photocurrent near-field microscopy, where near-field excited GPs are detected thermoelectrically rather than optically. This on-chip detection simplifies GP imaging as sophisticated s-SNOM detection schemes can be avoided. The photocurrent images reveal strongly reduced GP wavelengths (λp ≈ λ0/66), a linear dispersion resulting from the coupling of GPs with the metal gate below the graphene, and that plasmon damping at positive carrier densities is dominated by Coulomb impurity scattering.

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A.

TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNα) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRIM22's targeting of the HCV NS5A protein. NS5A is important for HCV replication and for resistance to IFNα therapy. During the first 24 h following the initiation of IFNα treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA (siRNA)-mediated knockdown of TRIM22 diminished IFNα-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFNα treatment and plays an important role in controlling HCV replication in vitro.

Electron optics with p-n junctions in ballistic graphene.

Electrons transmitted across a ballistic semiconductor junction are expected to undergo refraction, analogous to light rays across an optical boundary. In graphene, the linear dispersion and zero-gap band structure admit highly transparent p-n junctions by simple electrostatic gating. Here, we employ transverse magnetic focusing to probe the propagation of carriers across an electrostatically defined graphene junction. We find agreement with the predicted Snell's law for electrons, including the observation of both positive and negative refraction. Resonant transmission across the p-n junction provides a direct measurement of the angle-dependent transmission coefficient. Comparing experimental data with simulations reveals the crucial role played by the effective junction width, providing guidance for future device design. Our results pave the way for realizing electron optics based on graphene p-n junctions.

Near-field photocurrent nanoscopy on bare and encapsulated graphene.

Optoelectronic devices utilizing graphene have demonstrated unique capabilities and performances beyond state-of-the-art technologies. However, requirements in terms of device quality and uniformity are demanding. A major roadblock towards high-performance devices are nanoscale variations of the graphene device properties, impacting their macroscopic behaviour. Here we present and apply non-invasive optoelectronic nanoscopy to measure the optical and electronic properties of graphene devices locally. This is achieved by combining scanning near-field infrared nanoscopy with electrical read-out, allowing infrared photocurrent mapping at length scales of tens of nanometres. Using this technique, we study the impact of edges and grain boundaries on the spatial carrier density profiles and local thermoelectric properties. Moreover, we show that the technique can readily be applied to encapsulated graphene devices. We observe charge build-up near the edges and demonstrate a solution to this issue.

Evidence for a fractional fractal quantum Hall effect in graphene superlattices.

The Hofstadter energy spectrum provides a uniquely tunable system to study emergent topological order in the regime of strong interactions. Previous experiments, however, have been limited to low Bloch band fillings where only the Landau level index plays a role. We report measurements of high-mobility graphene superlattices where the complete unit cell of the Hofstadter spectrum is accessible. We observed coexistence of conventional fractional quantum Hall effect (QHE) states together with the integer QHE states associated with the fractal Hofstadter spectrum. At large magnetic field, we observed signatures of another series of states, which appeared at fractional Bloch filling index. These fractional Bloch band QHE states are not anticipated by existing theoretical pictures and point toward a distinct type of many-body state.

Replication Inhibition of Hepatitis B Virus and Hepatitis C Virus in Co-Infected Patients in Chinese Population.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infections contributes to a substantial proportion of liver disease worldwide. The aim of this study was to assess the clinical and virological features of HBV-HCV co-infection. METHODS: Demographic data were collected for 3238 high-risk people from an HCV-endemic region in China. Laboratory tests included HCV antibody and HBV serological markers, liver function tests, and routine blood analysis. Anti-HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBsAg-positive samples were tested for HBV DNA. RESULTS: A total of 1468 patients had chronic HCV and/or HBV infections. Among them, 1200 individuals were classified as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were classified as co-infected. The HBV-HCV co-infected patients not only had a lower HBV DNA positive rate compared to HBV mono-infected patients (84.1% versus 94.4%, respectively; P < 0.001). The median HCV RNA levels in HBV-HCV co-infected patients were significantly lower than those in the HCV mono-infected patients (1.18[Interquartile range (IQR) 0-5.57] versus 5.87[IQR, 3.54-6.71] Log10 IU/mL, respectively; P < 0.001). Furthermore, co-infected patients were less likely to have detectable HCV RNA levels than HCV mono-infected patients (23.4% versus 56.5%, respectively; P < 0.001). Those HBV-HCV co-infected patients had significantly lower median HBV DNA levels than those mono-infected with HBV (1.97[IQR, 1.3-3.43] versus 3.06[IQR, 2-4.28] Log10 IU/mL, respectively; P < 0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection group, and similar to that of the HCV mono-infected group. CONCLUSION: These results suggest that co-infection with HCV and HBV inhibits the replication of both viruses. The serologic results of HBV-HCV co-infection in patients suggests more liver injury compared to HBV mono-infected patients, but is similar to HCV mono-infection.